Modeling stem cell population growth: incorporating parameters for quiescence, differentiation and apoptosis

The use of stem cells in cell-mediated therapies or cell transplantation applications will require a controlled, scalable system for expansion of the cells and for control of cellular differentiation. Modeling stem cell population growth is one step towards developing such a system. Stem cell populations are heterogeneous and include cells which are non-mitotic. In particular, stem cells may be quiescent or mitotically active. The mitotically-active cells may 1) self-renew to give rise to similar cells, or 2) divide asymmetrically to give rise to precursor cells (which become may terminally differentiated). Cell populations also may include non-mitotic cells which are apoptotic. Non-exponential growth of the stem cell population is the result of the non-mitotic fraction. In this study, we extend a non-exponential model to incorporate parameters describing the non-dividing population. In particular, the models incorporate terms to account for 1) cell loss due to apoptosis or necrosis and 2) the non-dividing differentiated state of a cell. Murine muscle-derived stem cells (MDSC) will be used to experimentally test the model assumptions and determine the goodness of fit of the models using nonlinear regression. This analysis illustrates the dynamics of proliferation in stem cell populations where cells are undergoing both self-renewal and differentiation.